EFFECTS OF ATRIONATRIURETIC FACTOR ON CA2+ CURRENT AND CA(I)-INDEPENDENT TRANSIENT OUTWARD K+ CURRENT IN HUMAN ATRIAL CELLS

The effect of 10 nM atrial natriuretic peptide (ANF) on macroscopic L-type calcium current, I(Ca), and calcium-independent outward potassium current, I(lo), were studied in myocytes isolated from human atrial trabeculae using the whole-cell-recording patch-clamp technique. When cells were dialysed with pipette media containing 0.2 mM GTP, ANF reduced I(Ca). by 37.81% +/- 5.4% at +20 mV and I(lo) by 21.72% +/- 3.68% at +60 mV in a reversible manner. When I(Ca) was increased by beta-adrenoreceptor stimulation (0.1 muM isoproterenol) or by the phosphodiesterase inhibitor isobutylmethylxanthine (10 muM) ANF reduced I(Ca) by 24.99 +/- 3.4% and by 39.9 +/- 6.3% respectively. In cells dialysed with GTP-free pipette media, ANF increased I(Ca) markedly (39.8% +/- 7%) and reversibly, whereas it still depressed I(lo) (18.92% +/- 2%). Addition of 0.2 mM GTP[gammaS] to the pipette solution in the absence of GTP increased I(Ca), decreased I(lo) and suppressed the effect of ANF on both I(Ca) and I(lo). It is suggested that activation of the ANF receptor in human atrial cells reduces I(Ca) via guanylate-cyclase-dependent cGMP production, increases I(Ca) via Gs protein activation and decreases I(lo) via Gi protein activation.